Omicron infection increases IgG binding to spike protein of predecessor variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1 and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Residual archival sera (N = 81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N = 18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). We found an approximately two-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared with the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of the weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36%-49%) was observed to Omicron spike protein. Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants.

Virtual microscopy as a teaching-learning tool for histology in a competency-based medical curriculum.

Background: Histology forms an important component of first-year medical education. Unfortunately, it is limited to the practical laboratory due to the need for a microscope and good quality slides. Virtual microscopy is a recent advancement, which uses computers as an alternative to microscopes. The aim of the study was to compare virtual microscopy (VM)-based practical classes with traditional microscopy (TM)-based practical classes for two cohorts of first-year medical students, by comparing learning achieved using two different test scores as well as a qualitative assessment of student and faculty perspectives regarding the feasibility and usefulness of VM. Methods: Each cohort of students was divided into two equal batches and each batch underwent eight histology modules of which, four utilised traditional microscopes and four utilised virtual microscopes. Quantitative analysis was performed using a theory test (which assessed preparation, theory knowledge and understanding) as well as a spotter test (which assessed identification skills, reasoning, and recall). Qualitative analysis was performed using a structured questionnaire and focus group discussions. Results: Modules using VM were better when compared with those using TM, showing statistically significant and better grades. Qualitative analysis performed, yielded important information as to how this technology can serve as a good adjunct to traditional histology classes in the competency-based curriculum by increasing student interest, enabling self-study, and reducing students dependence on the tutor. Conclusions: VM forms a good adjunct as well as a standalone modality of learning to TM, as it improves accessibility to slides and promotes self-learning.

Functional principal component analysis for identifying the child growth pattern using longitudinal birth cohort data.

BACKGROUND: Longitudinal studies are important to understand patterns of growth in children and limited in India. It is important to identify an approach for characterising growth trajectories to distinguish between children who have healthy growth and those growth is poor. Many statistical approaches are available to assess the longitudinal growth data and which are difficult to recognize the pattern. In this research study, we employed functional principal component analysis (FPCA) as a statistical method to find the pattern of growth data. The purpose of this study is to describe the longitudinal child growth trajectory pattern under 3 years of age using functional principal component method. METHODS: Children born between March 2002 and August 2003 (n = 290) were followed until their third birthday in three neighbouring slums in Vellore, South India. Field workers visited homes to collect details of morbidity twice a week. Height and weight were measured monthly from 1 month of age in a study-run clinic. Longitudinal child growth trajectory pattern were extracted using Functional Principal Component analysis using B-spline basis functions with smoothing parameters. Functional linear model was used to assess the factors association with the growth functions. RESULTS: We have obtained four FPCs explained by 86.5, 3.9, 3.1 and 2.2% of the variation respectively for the height functions. For height, 38% of the children's had poor growth trajectories. Similarly, three FPCs explained 76.2, 8.8, and 4.7% respectively for the weight functions and 44% of the children's had poor growth in their weight trajectories. Results show that gender, socio-economic status, parent's education, breast feeding, and gravida are associated and, influence the growth pattern in children. CONCLUSIONS: The FPC approach deals with subjects' dynamics of growth and not with specific values at given times. FPC could be a better alternate approach for both dimension reduction and pattern detection. FPC may be used to offer greater insight for classification.

Cost of Illness Due to Severe Enteric Fever in India.

BACKGROUND: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden. METHODS: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting. RESULTS: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure. CONCLUSIONS: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed.

Natural History of Cryptosporidiosis in a Birth Cohort in Southern India.

BACKGROUND: Cryptosporidium is a leading cause of moderate to severe childhood diarrhea in resource-poor settings. Understanding the natural history of cryptosporidiosis and the correlates of protection are essential to develop effective and sustainable approaches to disease control and prevention. METHODS: Children (N = 497) were recruited at birth in semiurban slums in Vellore, India, and followed for 3 years with twice-weekly home visits. Stool samples were collected every 2 weeks and during diarrheal episodes were tested for Cryptosporidium species by polymerase chain reaction (PCR). Serum samples obtained every 6 months were evaluated for seroconversion, defined as a 4-fold increase in immunoglobulin G directed against Cryptosporidium gp15 and/or Cp23 antigens between consecutive sera. RESULTS: Of 410 children completing follow-up, 397 (97%) acquired cryptosporidiosis by 3 years of age. PCR identified 1053 episodes of cryptosporidiosis, with an overall incidence of 0.86 infections per child-year by stool and serology. The median age for the first infection was 9 (interquartile range, 4-17) months, indicating early exposure. Although infections were mainly asymptomatic (693 [66%]), Cryptosporidium was identified in 9.4% of diarrheal episodes. The proportion of reinfected children was high (81%) and there was clustering of asymptomatic and symptomatic infections (P < .0001 for both). Protection against infection increased with the order of infection but was only 69% after 4 infections. Cryptosporidium hominis (73.3%) was the predominant Cryptosporidium species, and there was no species-specific protection. CONCLUSIONS: There is a high burden of endemic cryptosporidiosis in southern India. Clustering of infection is suggestive of host susceptibility. Multiple reinfections conferred some protection against subsequent infection.

Prevalence and risk factors for scrub typhus in South India.

OBJECTIVE: To determine the prevalence and risk factors of scrub typhus in Tamil Nadu, South India. METHODS: We performed a clustered seroprevalence study of the areas around Vellore. All participants completed a risk factor survey, with seropositive and seronegative participants acting as cases and controls, respectively, in a risk factor analysis. After univariate analysis, variables found to be significant underwent multivariate analysis. RESULTS: Of 721 people participating in this study, 31.8% tested seropositive. By univariate analysis, after accounting for clustering, having a house that was clustered with other houses, having a fewer rooms in a house, having fewer people living in a household, defecating outside, female sex, age >60 years, shorter height, lower weight, smaller body mass index and smaller mid-upper arm circumference were found to be significantly associated with seropositivity. After multivariate regression modelling, living in a house clustered with other houses, female sex and age >60 years were significantly associated with scrub typhus exposure. CONCLUSIONS: Overall, scrub typhus is much more common than previously thought. Previously described individual environmental and habitual risk factors seem to have less importance in South India, perhaps because of the overall scrub typhus-conducive nature of the environment in this region.

Conditional random slope: A new approach for estimating individual child growth velocity in epidemiological research.

OBJECTIVES: Conditioning child growth measures on baseline accounts for regression to the mean (RTM). Here, we present the "conditional random slope" (CRS) model, based on a linear-mixed effects model that incorporates a baseline-time interaction term that can accommodate multiple data points for a child while also directly accounting for RTM. METHODS: In two birth cohorts, we applied five approaches to estimate child growth velocities from 0 to 12 months to assess the effect of increasing data density (number of measures per child) on the magnitude of RTM of unconditional estimates, and the correlation and concordance between the CRS and four alternative metrics. Further, we demonstrated the differential effect of the choice of velocity metric on the magnitude of the association between infant growth and stunting at 2 years. RESULTS: RTM was minimally attenuated by increasing data density for unconditional growth modeling approaches. CRS and classical conditional models gave nearly identical estimates with two measures per child. Compared to the CRS estimates, unconditional metrics had moderate correlation (r = 0.65-0.91), but poor agreement in the classification of infants with relatively slow growth (kappa = 0.38-0.78). Estimates of the velocity-stunting association were the same for CRS and classical conditional models but differed substantially between conditional versus unconditional metrics. CONCLUSION: The CRS can leverage the flexibility of linear mixed models while addressing RTM in longitudinal analyses.

Reduced rotavirus vaccine effectiveness among children born during the rotavirus season: a pooled analysis of 5 case-control studies from the Americas.

Using data from rotavirus vaccine effectiveness (VE) studies, we assessed whether rotavirus season modifies rotavirus VE in infants. In the first year of life, adjusted VE was 72% for children born during rotavirus season and 84% for children born in other months (P = .01). Seasonal factors may interfere with vaccine performance.

Influence of publicly funded conditional cash transfer programms on utilization patterns of healthcare services for acute childhood illness.

BACKGROUND: Conditional cash transfers are widespread and effective for utilization of targeted health services, but there is little evidence of their influence on the utilization of non-targeted or extended general healthcare services. Using data from a population-based health utilization survey, we evaluated the influence of conditional cash transfers for maternal and immunization services on the utilization of healthcare services for acute childhood illnesses. METHODS: Participants included mothers or primary caretakers of children <2 y of age residing in 2407 households in urban Vellore, Tamil Nadu, India. Mothers of children with illness in the preceding month were interviewed on presenting symptoms, provider choice and beneficiary status of maternal and immunization-based conditional cash transfer programs. RESULTS: Of 2407 children <2 y of age, about 48% reported being beneficiaries of maternal and immunization-based conditional cash transfers. Beneficiary status was associated with an increased use of public services (adjusted relative risk [aRR] 3.14 [95% confidence interval {CI} 1.96 - 5.02]) but not the use of private services (aRR 1.42 [95% CI 0.97 - 2.08]) relative to home or informal care. CONCLUSIONS: Our findings indicate financial incentives for use of maternal and immunization services could have an indirect, non-targeted effect on utilization of formal healthcare for acute childhood illnesses.

Iron homeostasis is dysregulated, but the iron-hepcidin axis is functional, in chronic liver disease.

BACKGROUND: Perturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved. METHODS: Patients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters. RESULTS: Patients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter-1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 µg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 µg/dL. CONCLUSIONS: In patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease.

Spousal Caregiver Burden and Its Relation with Disability in Schizophrenia.

BACKGROUND: Schizophrenia, a chronic psychiatric disorder, can affect one's productivity and psychosocial functioning. In Indian context, the responsibility of caring persons with schizophrenia is increasingly on their spouses. Spousal caregiver experience and its relation with disability in schizophrenia need to be studied. MATERIALS AND METHODS: We conducted a cross-sectional study among 52 outpatients with schizophrenia and their spouses attending a tertiary psychiatric center. The objectives were: (a) to explore spousal caregiver burden in schizophrenia and (b) to assess the relation between disability and spousal caregiver burden. The study adopted recommended ethical principles. Scales such as Burden Assessment Schedule, Indian Disability Evaluation and Assessment Scale (IDEAS), and Positive and Negative Syndrome Scale were used to collect appropriate data. Descriptive analysis, bivariate analysis, and multivariate analysis were done in SPSS software version 16.0. RESULTS: The mean spousal caregiver burden score was 73.5 (standard deviation: 14.0). In bivariate analysis, disability, duration of schizophrenia, severity of schizophrenia, place of residence, and socioeconomic status had statistically significant relation with spousal caregiver burden. Adjusted for spouses' age, gender, and other significant factors in bivariate analysis, the IDEAS global disability score (2.6, [confidence interval 0.5-3.8, P = 0.013]) retained statistically significant association with spousal caregiver burden. CONCLUSION: Spouses of persons with schizophrenia experience significant caregiver burden. Disability was found to be the most powerful determinant of spousal caregiver burden in the sample. Focus on disability alleviation in the management of schizophrenia may help reduce spousal caregiver burden.

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results.

Exclusive breastfeeding practices among mothers in urban slum settlements: pooled analysis from three prospective birth cohort studies in South India.

BACKGROUND: The World Health Organization (WHO) recommends six months of exclusive breastfeeding. Despite documented health, social and economic benefits, the practice of exclusive breastfeeding is quite low and information on influencing factors is limited especially from slum settlements. Our goal is to assess the prevalence and evaluate factors associated with early cessation of exclusive breastfeeding in the first six months of life among mothers in urban slums of Vellore, Southern India. METHODS: We pooled data from three similar birth cohort studies (n = 1088) conducted between 2002 and 2009. Breastfeeding information was obtained soon after birth and then from follow-up home visits conducted once every two weeks by the field workers. Multivariable Cox regression analyses were used to assess factors associated with early cessation of exclusive breastfeeding. RESULTS: The prevalence of exclusive breastfeeding for the first six months was 11.4%, based on prospective data since birth. Results from multivariable analyses revealed maternal education (Adjusted Hazard Ratio [AHR] 1.18 , 95% CI 1.03, 1.35), pucca type of house (AHR 1.25 , 95% CI 1.10, 1.43), two or more number of children in the family (AHR 1.26 , 95% CI 1.10, 1.43), joint family structure (AHR 1.20 , 95% CI 1.02, 1.40) and birth during summer (AHR 1.16, 95% CI 1.01, 1.31) were associated with early cessation of exclusive breastfeeding in the first six months. CONCLUSIONS: Our results indicate that exclusive breastfeeding rates are well below the recommended levels. Educational interventions providing comprehensive breastfeeding information to mothers and their families can be evaluated to assess its effect on improving infant feeding practices.

Patient Experience with Conscious Sedation as a Method of Pain Relief for Transvaginal Oocyte Retrieval: A Cross Sectional Study.

AIM: The aim of the study was to measure patient's satisfaction level and acceptance of conscious sedation as a method of pain relief following transvaginal oocyte retrieval (TVOR) during assisted reproduction technology treatment. We also evaluated the factors that may influence the efficacy of conscious sedation method. SETTING AND DESIGN: A prospective cross-sectional study. MATERIALS AND METHODS: Prospective study was conducted from October 2015 to January 2016 at a university-level hospital and 100 women were recruited. Variables for analysis included woman age, duration of procedure, number of oocytes retrieved, and transmyometrial passage of the needle. Pain assessment was done by visual analog scale (VAS). Medical complications, and patient satisfaction score [Likert's score and client satisfaction questionnaire (CSQ)] were recorded. RESULTS: There was a moderate positive correlation between age and pain score on day 1 post-procedure. When the duration of procedure was >12 min, immediate post-procedure pain score was significantly higher compared to those whose procedure where duration was <12 min. There was no correlation between pain score and the number of oocytes retrieved (≤5, 6-15, and ≥16) and transmyometrial passage of needle. The VAS 10-point score immediately post-procedure, after 6 and 24 h post-procedure, and on day of embryo transfer was 2.83 (±1.67), 0.78 (±1.04), 0.39 (±1.09), and 0.14 (±0.58), respectively. The Likert's score was 3.65 (±0.82) and mean CSQ was 27.04 (±3.01). Majority of the women (86%) preferred the same pain relief method for future analgesia. There were no major complications. CONCLUSION: Conscious sedation was associated with high satisfaction level and acceptance rate among patients undergoing TVOR.

Estimating the incidence of rotavirus infection in children from India and Malawi from serial anti-rotavirus IgA titres.

Accurate estimates of rotavirus incidence in infants are crucial given disparities in rotavirus vaccine effectiveness from low-income settings. Sero-surveys are a pragmatic means of estimating incidence however serological data is prone to misclassification. This study used mixture models to estimate incidence of rotavirus infection from anti-rotavirus immunoglobulin A (IgA) titres in infants from Vellore, India, and Karonga, Malawi. IgA titres were measured using serum samples collected at 6 month intervals for 36 months from 373 infants from Vellore and 12 months from 66 infants from Karonga. Mixture models (two component Gaussian mixture distributions) were fit to the difference in titres between time points to estimate risk of sero-positivity and derive incidence estimates. A peak incidence of 1.05(95% confidence interval [CI]: 0.64, 1.64) infections per child-year was observed in the first 6 months of life in Vellore. This declined incrementally with each subsequent time interval. Contrastingly in Karonga incidence was greatest in the second 6 months of life (1.41 infections per child year [95% CI: 0.79, 2.29]). This study demonstrates that infants from Vellore experience peak rotavirus incidence earlier than those from Karonga. Identifying such differences in transmission patterns is important in informing vaccine strategy, particularly where vaccine effectiveness is modest.